Phase 3 · Semaglutide

PIONEER 12 trial results

China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

Participants
1,441
Status
completed
Completed
2021-10-27
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT04017832), updated at source Oct 1, 2024. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What PIONEER 12 measured first

Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%)Percentage point of HbA1C · From baseline to week 26 · mean
MeasureOral Semaglutide 3 mgn=344Oral Semaglutide 7 mgn=340Oral Semaglutide 14 mgn=332Sitagliptin 100 mgn=350
On-treatment observation period-0.8(1.0)-1.3(1.0)-1.6(1.0)-0.7(1.0)
In-trial observation period-0.8(1.0)-1.3(1.0)-1.5(1.0)-0.7(1.0)
Side effects by arm

Side effects in PIONEER 12

Percent of participants affected, From baseline to week 31. The most common events the registry lists.

EventOral Semaglutide 3 mgOral Semaglutide 7 mgOral Semaglutide 14 mgSitagliptin 100 mg
Any serious event4.4%3.1%3%4.2%
Diarrhoea8.3%8.9%13.3%4.5%
Nausea10%10.9%12.2%3.9%
Decreased appetite6.1%8.4%9.4%1.4%
Upper respiratory tract infection7.2%7%8.6%7.8%
Vomiting4.4%5%8%0.3%
Lipase increased4.2%4.7%5.8%3.4%
Secondary outcomes

What else it measured

Change From Baseline to Week 26 in Fasting Plasma Glucose (FPG)mmol/l · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=322Oral Semaglutide 7 mgn=317Oral Semaglutide 14 mgn=294Sitagliptin 100 mgn=329
-1.03(2.11)-1.79(2.20)-2.00(2.42)-0.52(2.36)
Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profilemmol/L · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=300Oral Semaglutide 7 mgn=311Oral Semaglutide 14 mgn=290Sitagliptin 100 mgn=317
-1.5(2.2)-2.3(2.2)-2.6(2.2)-1.2(2.4)
Change From Baseline to Week 26 in 7 Point SMPG Profile: Mean Postprandial Increment (Over All Meals)mmol/L · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=301Oral Semaglutide 7 mgn=311Oral Semaglutide 14 mgn=290Sitagliptin 100 mgn=317
-0.4(2.0)-0.9(1.9)-1.0(2.1)-0.6(2.1)
Number of Participants Who Achieved HbA1c <7.0 % (53 mmol/Mol) (American Diabetes Association [ADA] Target) (Yes/no)Participants · At week 26 · count of participants
MeasureOral Semaglutide 3 mgn=321Oral Semaglutide 7 mgn=315Oral Semaglutide 14 mgn=298Sitagliptin 100 mgn=334
Yes139213226122
No18210272212
Number of Participants Who Achieved HbA1c Equal to or Below 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no)Participants · At week 26 · count of participants
MeasureOral Semaglutide 3 mgn=321Oral Semaglutide 7 mgn=315Oral Semaglutide 14 mgn=298Sitagliptin 100 mgn=334
Yes8116118854
No240154110280
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) (Yes/no)Participants · At week 26 · count of participants
MeasureOral Semaglutide 3 mgn=321Oral Semaglutide 7 mgn=314Oral Semaglutide 14 mgn=298Sitagliptin 100 mgn=334
Yes141203226129
No18011172205
Time to Rescue MedicationParticipants · From baseline to week 31 · count of participants
Oral Semaglutide 3 mgn=361Oral Semaglutide 7 mgn=360Oral Semaglutide 14 mgn=361Sitagliptin 100 mgn=359
5667
Change From Baseline to Week 26 in Body Weight (Kilogram [kg])Kilogram · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=322Oral Semaglutide 7 mgn=319Oral Semaglutide 14 mgn=300Sitagliptin 100 mgn=335
-1.4(3.0)-2.9(3.3)-3.8(3.7)-0.5(2.6)
Percentage Change From Baseline to Week 26 in Body WeightPercentage change · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=322Oral Semaglutide 7 mgn=319Oral Semaglutide 14 mgn=300Sitagliptin 100 mgn=335
-2(4)-4(4)-5(5)-1(3)
Change From Baseline to Week 26 in Body Mass Index (BMI)Kilogram per square meter (kg/m^2) · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=322Oral Semaglutide 7 mgn=319Oral Semaglutide 14 mgn=300Sitagliptin 100 mgn=335
-0.5(1.1)-1.1(1.2)-1.4(1.3)-0.2(0.9)
Change From Baseline to Week 26 in Waist CircumferenceCentimeter · From baseline to week 26 · mean
Oral Semaglutide 3 mgn=322Oral Semaglutide 7 mgn=320Oral Semaglutide 14 mgn=300Sitagliptin 100 mgn=335
-1.6(4.0)-2.7(4.4)-3.7(4.1)-0.8(3.4)
Change From Baseline to Week 26 in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)Ratio of total cholesterol · From baseline to week 26 · geometric mean
Oral Semaglutide 3 mgn=316Oral Semaglutide 7 mgn=316Oral Semaglutide 14 mgn=296Sitagliptin 100 mgn=330
1.00(15.78)0.96(17.34)0.96(17.86)0.99(19.69)
The trial

How PIONEER 12 was run

This study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and sitagliptin (a medicine doctors can already prescribe). Participants will either get oral semaglutide or sitagliptin - which treatment is decided by chance. Participants will get 2 tablets a day to take first thing in the morning on an empty stomach. Only 1 tablet has study medicine in it. The other tablet is a dummy medicine (placebo). After taking the semaglutide tablet, participants may not eat or drink anything for at least 30 minutes. After the 30 minutes, participants must take the sitagliptin tablet. Then participants can have their first meal of the day and take any other medicines they may need, including their metformin. The study will last for about 7 months (33 weeks). Participants will have 8 clinic visits and 1 phone call with the study doctor. At all 8 of the clinic visits, participants will have blood samples taken.

  • Oral semaglutide 3 mg and placebo (sitagliptin): Oral semaglutide tablets 3 mg and sitagliptin placebo tablets for 26 weeks
  • Oral semaglutide 7 mg and placebo (sitagliptin): Oral semaglutide tablets and sitagliptin placebo tablets. The dose of oral semaglutide will be escalated over 4 weeks, after which the target dose of 7 mg is taken for 22 weeks
  • Oral semaglutide 14 mg and placebo (sitagliptin): Oral semaglutide tablets and sitagliptin placebo tablets. The dose of oral semaglutide will be escalated over 8 weeks, after which the target dose of 14 mg is taken for 18 weeks
  • Sitagliptin 100 mg and placebo (oral semaglutide): Sitagliptin tablets and oral semaglutide placebo tablets for 26 weeks
Who could join the trial

Inclusion Criteria: * Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male or female, age above or equal to 18 years at the time of signing informed consent. For Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent. For Taiwan only: Male or female, age above or equal to 20 years at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus 60 days or more prior to day of screening. * HbA1c between 7.0-10.5% (53-91 mmol/mol) (both inclusive). * Stable daily dose of metformin (equal to or above 1500 mg or maximum tolerated dose as documented in the subject medical record) 60 days or more prior to day of screening Exclusion Criteria: * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method (adequate contraceptive measure as required by local regulation or practice). * Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC). Family is defined as a first degree relative. * History or presence of pancreatitis (acute or chronic). * History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery). * Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation. * Subjects presently classified as being in New York Heart Association (NYHA) Class IV. * Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. * Renal impairment measured as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). * Subjects with alanine aminotransferase (ALT) above 2.5 x upper limit of the normal (ULN). * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation. Fundus examination without dilation is only allowed if the digital camera used for fundus photography has this feature. * Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.

Published papers

Papers from PIONEER 12

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.